Cytochrome P450 2J2 Metabolism of Anandamide in a K562 Human Cell Line
Hammar, Dagan K.
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Cytochrome P450 2J2 (CYP2J2) is a heme-‐containing enzyme primarily found in the cardiovascular system, specifically endothelial cells and cardiomyocytes. Additionally, CYP2J2 is expressed in various hematologic malignant diseases and in human tumor tissues and cell lines. CYP2J2 is known to metabolize arachidonic acid (AA) to four epoxyeicosatrienoic acids (EETs). These EETs have been shown to inhibit tumor cell apoptosis while increasing cell proliferation. Inhibition of CYP2J2 activity has been shown to decrease tumor cell growth and increase cell death. Anandamide (AEA), an N-‐acyl-‐ethanolamine with a structure similar to that of AA, is known to be antiproliferative while inhibiting the processes of migration, invasion, and angiogenesis. Studies were conducted to determine if AEA was a substrate for CYP2J2. Because AA is known to inhibit other P450’s activity, a study to determine if AA would compete with AEA for CYP2J2 metabolism was completed. The studies reported here determined that CYP2J2, in a human leukemia cell line (K562), metabolized AEA to form four epoxygenated products, 5,6-‐, 8,9-‐, 11,12-‐, and 14,15-‐ epoxyeicosatrienoic acid ethanolamides (EET-‐EA) and a hydroxylated product, 19-‐ hydroxyeicosatraenoic acid ethanolamide (HETE-‐EA) Results suggest the involvement of CYP2J2 in the metabolism of AEA, but show that it is not the major P450 responsible for AEA metabolism in K562 cells. In addition, AEA was determined not to inhibit P450 activity, unlike AA.